The objective is to continue development of MIT's interdisciplinary predoctoral graduate training program in Computational and Systems Biology (CSB) which trains students to become leaders in biomedical research at the interface of biology, computation and engineering. The CSB Ph.D. program is a core component of MIT's Computational and Systems Biology Initiative (CSBi;.http://csbi.mit.edu), an institute-wide initiative that spans a variety of collaborative and interdisciplinary research, educational and community efforts in the field. Program faculty are concentrated inthe three founding departments - Biological Engineering (BE), Biology, and Electrical Engineering & Computer Science (EECS) - with additional involvement of faculty from other departments. Faculty from these departments have research programs spanning a broad set of topics in computational and systems biology, including gene and protein network modeling and reconstruction, cell and tissue engineering, bioimaging and image informatics, regulatory genomics, proteomics, predictive toxicology and metabolic engineering, nanobiology and microsystems, computational biophysics, and integrative cancer biology. This proposal seeks to expand the pool of training faculty by more than a dozen, including 7 faculty newly hired in the past 4 years who have active research programs in the field. Students apply directly to the CSB Ph.D program from their undergraduate or Master's institution and receive multi- and nter-disciplinary training in the field of computational and systems biology. The proposal seeks to support 8 students for the first two years of the Ph.D., enabling extended research rotations and participation in unique program activities. Unique aspects of the program include: (a) close association with the multi- and inter-disciplinary research agenda of SBi and of the participating labs;(b) a unique core formed from newly developed, inter-disciplinary classroom subjects that combine biology, engineering, statistics and computation;(c) intensive advising and multi-disciplinary thesis committees to optimize the training experience for students from diverse academic backgrounds;(d) a seminar series program with active student participation focusing on leading edge research both within and outside of MIT;(e) an annual symposium and an annual retreat with participation of students and faculty focusing on research, leadership, and challenges to interdisciplinary research. PERFORMANCE SITE(S) (organization, city, state) MIT Whitehead Broad Institute Relevance. The proposed training program will enable training of a new type of researcher, with interdisciplinary expertise in concepts, approaches and technologies from biology, computer science, and engineering. This new group will be ideally positioned to assume leadership positions in biomedical research, which increasingly involves the application of sophisticated technologies and advanced modeling techniques to design and predict sites of intervention in complex gene networks to achieve desired therapeutic aims in diseases such as diabetes and cancer. PHS 398/2590 (Rev.11/07) Page o Continuation Format Page Principal Investigator/Program Director (Last, First, Middle): Burge, Christopher (Continuation from Cover Pages) SCIENTIFIC/KEY PERSONNEL. See instructions. Use continuation pages as neededto provide the required information in the format shown below. Start with Program Director(s)/Principal Investigator(s). List all other key personnel in alphabetical order, last name first. Name eRA Commons User Name Organization Role on Project Burge, Christopher cburge MIT PI Aim, Eric ajalm MIT Mentor Bartel, David dbartel MIT Mentor Boyer, Laurie laboyer MIT Mentor Chisholm, Sallie chisholm MIT Mentor Drennan, Catherine cdrennan MIT Mentor Fraenkel, Ernest fraenkel MIT Mentor Gifford, David dkg MIT Mentor Griffith, Linda griffith MIT Mentor Grossman, Alan agd MIT Mentor Jasanoff, Alan jasanoff MIT Mentor Keating, Amy keating MIT Mentor Kellis, Manolis manoli MIT Mentor Klibanov, Alexander klibanov MIT Mentor Lander, Eric elander MIT Mentor Laub, Michael mlaubl MIT Mentor Lauffenburger, Douglas lauffenburger MIT Mentor Manalis, Scott srmOOl MIT Mentor Matsudaira, Paul matsudaira MIT Mentor Regev, Aviv regev MIT Mentor Samson, Leona Isamson MIT Mentor Sauer, Robert bobsauer MIT Mentor Seung, Sebastian SEUNG1 MIT Mentor Sharp, Phillip sharppa MIT Mentor Stultz, Collin cmstultz MIT Mentor Tidor, Bruce tidoM MIT Mentor Trout, Bernhardt trout MIT Mentor Van Oudenaarden, Alexander avano MIT Mentor Voldman, Joel voldman MIT Mentor White, Forest fwhitemit MIT Mentor Yaffe, Michael yaffe MIT Mentor Yanik, Mehmet Fatih MYANIK MIT Mentor Young, Richard young MIT Mentor PHS 398/2590 (Rev. 11/07) Page Continuation Format Page Institutional Training TOC Program Director/Principal Investigator Surge, Christopher Substitute Page (Last, first, middle): Type the name of the program director/principal investigator at the top of each printed page and each continuation page. (For type specifications, see PHS 398 Instructions.) INSTITUTIONAL RESEARCH TRAINING INCLUDING RUTH L. KIRSCHSTEIN NATIONAL RESEARCH SERVICE AWARD TABLE OF CONTENTS (Substitute Page) Page Numbers Face Page (Form Page 1) 1_ Description,